Of the approximately 350,000 total joint replacements that are currently performed in the U.S. each year, a significant number will require premature revision operation. One of the most challenging diagnostic aspects of the painful implant is the differentiation between aseptic osteolysis, an inflammatory response to infiltration of wear debris, and infection of the tissue surrounding the joint. Current diagnostic techniques such as plain radiography, laboratory and nuclear medicine tests have severe shortcomings. At the same time, failed diagnosis of infection can dramatically worsen the outcome of a revision operation with sharply increased morbidity and mortality, and underestimation of the extent of aseptic osteolysis may lead to wrong timing of the revision. Both Computed Tomography (CT) and Positron Emission Tomography (PET) have been recognized as potential diagnostic alternatives with excellent sensitivity and specificity for both conditions. However, CT suffers from severe image artifacts in the presence of metallic implants that not only render the CT images undiagnostic but also negatively influence the usability of PET data when they are obtained with modern multimodality PET/CT equipment. In a pilot study at our institution on a dedicated imaging phantom, algorithmic reduction of CT metal artifact was shown to be effective for CT-based diagnosis of aseptic osteolysis. The main objective of the proposed research is to extend this work to PET/CT and thereby create a novel one-stop diagnostic tool for both aseptic osteolysis and infection. The experimental focus of this proposal is to build an osteolysis and infection phantom simulator to optimize and test our metal artifact reduction algorithms, and to test the hypothesis that a combination PET/CT scan is more useful than standalone PET in a small study of 20 patients with painful hip or knee prostheses. Furthermore, based on follow-up CT imaging we will for the first time be able to assess progression rates of aseptic osteolysis directly next to the implant. We believe that a novel metal artifact-corrected PET/CT scan will ensure patient safety by providing a differential diagnosis of both aseptic osteolysis and infection and will help improve surgical planning and avoid misdiagnosis of osteolysis and infection with its painful and costly consequences. PUBLIC HEALTH RELEVANCE: Joint replacement with artificial hips and knees has become a very successful surgical choice to treat osteoarthritis and other joint diseases. Because of the large number of patients so treated, the small fraction of implants that develop painful loosening results in a large rate of patients needing to undergo revision surgery. It is important to correctly diagnose the complication causing the pain to ensure optimal patient management and surgical planning. We propose to overcome the technical challenges associated with using X-ray computed tomography for imaging of metallic implants and use the technique in combination with Positron Emission Tomography to provide a novel comprehensive tool for the early diagnosis of the complications that would otherwise lead to implant failure. [unreadable] [unreadable] [unreadable]